NM_024782.3(NHEJ1):c.547C>T (p.Pro183Ser) AND Cernunnos-XLF deficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 27, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001904111.6

Allele description [Variation Report for NM_024782.3(NHEJ1):c.547C>T (p.Pro183Ser)]

NM_024782.3(NHEJ1):c.547C>T (p.Pro183Ser)

Gene:

NHEJ1:non-homologous end joining factor 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q35

Genomic location:

Preferred name:

NM_024782.3(NHEJ1):c.547C>T (p.Pro183Ser)

HGVS:

NC_000002.12:g.219146721G>A
NG_007880.1:g.19145C>T
NM_001377498.1:c.547C>T
NM_001377499.1:c.547C>T
NM_024782.3:c.547C>TMANE SELECT
NP_001364427.1:p.Pro183Ser
NP_001364428.1:p.Pro183Ser
NP_079058.1:p.Pro183Ser
LRG_90:g.19145C>T
NC_000002.11:g.220011443G>A
NR_165304.1:n.643C>T

Protein change:

P183S

Links:

dbSNP: rs372722590

NCBI 1000 Genomes Browser:

rs372722590

Molecular consequence:

NM_001377498.1:c.547C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001377499.1:c.547C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_024782.3:c.547C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_165304.1:n.643C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Cernunnos-XLF deficiency (IMD124)
Synonyms:: SCID, AUTOSOMAL RECESSIVE, T CELL-NEGATIVE, B CELL-NEGATIVE, NK CELL-POSITIVE, WITH MICROCEPHALY, GROWTH RETARDATION, AND SENSITIVITY TO IONIZING RADIATION; NHEJ1 SYNDROME; Severe combined immunodeficiency with sensitivity to ionizing radiation due to NHEJ1 deficiency; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012650; MedGen: C1969799; Orphanet: 169079; OMIM: 611291

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002118154	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 27, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002118154

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 27, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002118154.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with NHEJ1-related conditions. This variant is present in population databases (rs372722590, gnomAD 0.007%). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 183 of the NHEJ1 protein (p.Pro183Ser).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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